Metoclopramide
| Evidence Level: L4 | Predicted Indications: 5 |
Table of Contents
Metoclopramide: From Gastroesophageal Reflux Disease to Gastric Ulcer
One-Sentence Summary
Metoclopramide is a prokinetic and antiemetic drug, originally used for gastroesophageal reflux disease and reflux (peptic) esophagitis. The TxGNN model predicts it may be effective for gastric ulcer, but the supporting evidence is weak: 1 clinical trial (indirectly relevant) and 20 publications (mostly general reviews of prokinetic drugs) are currently linked to this prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gastroesophageal reflux disease, esophagitis, peptic esophagitis (from the knowledge graph; no approved-indication text is available for the New Zealand licences) |
| Predicted New Indication | Gastric ulcer |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no currently valid licences) |
| Number of Authorizations | 2 (both cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on the pharmacology data, metoclopramide acts on dopamine D2 receptors, 5-HT4 receptors and 5-HT3 receptors. It is used as an antiemetic, to treat gastroesophageal reflux disease and to speed gastric emptying. It is a prokinetic drug: D2 antagonism combined with 5-HT4 agonism enhances gastric emptying and can reduce duodenogastric and gastroesophageal reflux.
The link to gastric ulcer is therefore indirect. Delayed gastric emptying or alkaline (bile) reflux may add to symptoms in some ulcer patients, so a prokinetic is plausible as a symptom-oriented adjunct. However, there is no evidence that metoclopramide heals ulcers. Acid suppression and H. pylori eradication remain the standard of care. The only supportive laboratory finding is an older rat study (PMID 2730234) reporting ulcer-protective effects in aspirin-induced and pylorus-ligated models, which has not been confirmed in humans. The high TxGNN score is a computational prediction and should be treated as a hypothesis only.
Other predicted indications are weaker still:
- Gastroduodenitis (99.90%): supported only by physiological and animal motility studies. Evidence level L4.
- Peptic ulcer disease (99.85%): indirect evidence only. Evidence level L4.
- Gastrojejunal ulcer (99.78%): no specific studies. Evidence level L5.
- Peptic ulcer perforation (99.78%): a prokinetic has no plausible role here and could be unsafe. This is likely a propagation artefact. Evidence level L5.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05746377 | Phase 4 | Unknown | 60 | Double-blind randomized trial of metoclopramide premedication before endoscopy in upper GI bleeding. It tests whether it reduces repeat endoscopy or need for intervention and improves visualization. This is an adjunctive diagnostic use, not ulcer treatment. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 786607 | 1976 | Review | Drugs | Pharmacology and clinical use of metoclopramide, including easing emergency endoscopy in upper GI haemorrhage |
| 579607 | 1978 | Review | Canadian Journal of Surgery | Symposium on medical treatment of peptic ulcer; notes that metoclopramide hastens gastric emptying |
| 2730234 | 1989 | Preclinical (rat) | Arch Int Pharmacodyn Ther | Ulcer-protective and antisecretory effects in aspirin-induced and pylorus-ligated gastric ulcer models, compared with ranitidine |
| 6782467 | 1981 | Randomized crossover study | MMW Munch Med Wochenschr | In 12 healthy men, metoclopramide and domperidone did not significantly change serum gastrin or gastric acid secretion |
| 7017896 | 1981 | Review | Scand J Gastroenterol Suppl | Therapeutic options for duodeno-gastric reflux, including drugs that enhance gastric emptying |
| 8095331 | 1993 | Review | Postgraduate Medicine | Strategies for ulcers and reflux esophagitis that resist standard regimens |
| 38059896 | 2024 | RCT | Am J Gastroenterol | Double-blind RCT of metoclopramide for gastric visualization at endoscopy in active upper GI bleeding |
| 42259699 | 2026 | RCT | Rev Gastroenterol Mex | Triple-blind trial of high-dose IV metoclopramide versus placebo for visualization in acute upper GI bleeding |
| 1551349 | 1992 | Randomized, double-blind physiological study | Dig Dis Sci | In 20 patients with erosive reflux esophagitis, metoclopramide and domperidone did not improve esophageal peristalsis or acid clearance |
| 42127996 | 2026 | Guideline | Endoscopy | ESGE 2026 guideline on peptic ulcer bleeding; a management guideline that does not itself show a role for metoclopramide in ulcer treatment |
Most of the remaining retrieved literature consists of general reviews on prokinetics, dyspepsia and gastroparesis. None shows that metoclopramide heals gastric ulcers.
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2690497 | Medsurge | Inj 5 mg per ml, 2 ml ampoule | Not available (status: cancelled) |
| 2528878 | Metoclopramide Actavis 10 | Tab 10 mg | Not available (status: cancelled) |
Cytotoxicity
Not applicable. Metoclopramide is not an antineoplastic drug, so this section is omitted.
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the current package insert for safety information.
- Contraindication-related conditions (knowledge graph): The drug-disease contraindication links in the TxGNN knowledge graph, which are not label text, flag the following conditions:
- Neurological and movement disorders: epilepsy, Parkinson disease and parkinsonian disorders, tardive dyskinesia, torsion dystonia, neuroleptic malignant syndrome
- Cardiovascular and endocrine: hypertension, pheochromocytoma and related adrenal or paraganglioma tumours
- Gastrointestinal: active peptic ulcer disease
- Organ function: cirrhosis of liver, impaired renal function
- Metabolic: porphyria, methaemoglobinaemia due to methaemoglobin reductase deficiency
- Psychiatric: anxiety, neurotic and dysthymic disorders
- Special concern for this indication: Because increased GI motility is undesirable when perforation or obstruction is suspected, a prokinetic should not be used in suspected perforation.
- Receptor pharmacology: Pharmacology records list D2, 5-HT4 and 5-HT3 receptor activity. Specific drug-drug interaction data are not available.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a high model score, but no study shows that metoclopramide heals gastric ulcers. The only trial concerns pre-endoscopy gastric visualization, the literature is indirect, and the drug has no currently valid licence in New Zealand. The evidence level is L4, and the knowledge graph lists active peptic ulcer disease among the contraindication-related conditions.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications, which block any safety screening
- Mechanism of action data (for example from DrugBank)
- Clinical evidence of benefit in gastric ulcer, for example a controlled trial of symptoms or healing, or a clear rationale for an adjunctive role
- Clarification of the knowledge graph contraindication for active peptic ulcer disease
- Confirmation of whether any metoclopramide product is currently marketed in New Zealand, since both licences are cancelled
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.